Transcriptional Regulation by NPAS4

NPAS4 (Neuronal PAS domain containing protein 4) is a calcium dependent transcription factor predominantly expressed in neurons that regulates activation of genes involved in neuronal circuit formation, function, and plasticity. NPAS4 possesses a conserved basic helix loop helix (bHLH) motif and a PAS domain. NPAS4 is among the most rapidly induced immediate early genes (IEGs), which are activated after sensory and behavioral experience and thought to be crucial for formation of long term memory. NPAS4 is activated within minutes of neuronal stimulation to regulate the formation of inhibitory synapses. Transcriptional targets of NPAS4 include transcription factors and proteins involved in signal transduction and protein trafficking. NPAS4 regulates development of glutamatergic and GABAergic synapses essential for information processing and memory formation. NPAS4 induced gene expression programs differ between excitatory and inhibitory neurons, leading to a circuit wide homeostatic response. Besides directly regulating function of neurons, NPAS4 may be involved in the regulation of neuroinflammation and neuronal apoptosis. NPAS4 is expressed in the pancreatic beta cells and regulates their function under stress conditions. For review, please refer to Sun and Lin 2016, and Fu et al. 2020.

Summary from Reactome (R-HSA-9634815), read 2026-09-23.